The D vitamins are important agents for the control of calcium and phosphate metabolism in animals and humans. They have long been used as dietary supplements and in clinical practice to assure proper bone growth and development. It is now known that the in vivo activity of these vitamins is dependent on hydroxylated forms of the vitamin. Especially important in this context are 1.alpha.-hydroxylated vitamin D derivatives. Further, it has also been learned that side chain structures are important in effecting vitamin D's biological activity.
Many processes for the preparation of vitamin D compounds have been reported in the literature. Among them are processes employing steroid aldehydes as precursors for the synthesis of vitamin D metabolites, or of side chain modified analogs [see, for example, Yamada et al., Tetrahedron Letters, 22, 2591-94 (1981); Sardina, et al., Tetrahedron Letters 24, 4477-4480 (1983); Morzycki et al., J. Org. Chem. 49, 2148 (1984); Sai et al., Chem Pharm. Bull. 34, 4508-15 (1986)]. After coupling the steroid aldehyde with a selected side chain fragment, one can then create the vitamin D triene system, and by means of regio- and stereoselective 1-alpha-hydroxylation produce the resulting 1-alpha-hydroxyvitamin. This approach involves a multi-step generation of the triene system, a process which together with the 1-alpha-hydroxylation sequence, must be repeated every time a new analog is to be synthesized.
Likewise, certain side chain alcohols, aldehydes or esters, containing a vitamin D nucleus, have been used for the preparation of vitamin D.sub.3 -derived metabolites or analogs by attachment of a side chain residue via Grignard-type reactions [U.S. Pat. No. 4,512,925; Andrews et al., J. Org. Chem. 51, 4819-4828 (1986)].